Search

Background and objectives For older patients with kidney failure, lowering symptom burden may be more important than prolonging life. Dialysis initiation may affect individual kidney failure-related symptoms differently, but the change in symptoms before and after start of dialysis has not been studied. Therefore, we investigated the course of total and individual symptom number and burden before and after starting dialysis in older patients.Design, setting, participants, & measurements The European Quality (EQUAL) study is an ongoing, prospective, multicenter study in patients >= 65 years with an incident eGFR

Introduction: Predicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically useful and relevant. We aimed to externally validate a recently developed CKD G4+ risk calculator for these outcomes and to assess its potential clinical impact in guiding vascular access placement. Methods: We included 1517 patients from the European Quality (EQUAL) study, a European multicentre prospective cohort study of nephrology-referred advanced CKD patients aged ≥65 years. Model performance was assessed based on discrimination and calibration. Potential clinical utility for timing of referral for vascular access placement was studied with diagnostic measures and decision curve analysis (DCA). Results: The model showed a good discrimination for KRT and “death after KRT,” with 2-year concordance (C) statistics of 0.74 and 0.76, respectively. Discrimination for cardiovascular events (2-year C-statistic: 0.70) and overall death (2-year C-statistic: 0.61) was poorer. Calibration was fairly accurate. Decision curves illustrated that using the model to guide vascular access referral would generally lead to less unused arteriovenous fistulas (AVFs) than following estimated glomerular filtration rate (eGFR) thresholds. Conclusion: This study shows moderate to good predictive performance of the model in an older cohort of nephrology-referred patients with advanced CKD. Using the model to guide referral for vascular access placement has potential in combating unnecessary vascular surgeries.

Background Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation in patients with advanced CKD is lacking, and most do not account for competing risks. Methods To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration. Results The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average c statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%-\18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts. Conclusions Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years).

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (≥65 years; estimated glomerular filtration rate ≤20 mL/min/1.73 m2) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off ≤70; 0–100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was –0.12 mL/min/1.73 m2/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03–1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men.

Malnutrition inflammation syndrome is common in chronic hemodialysis patients and may correlate with increased morbidity and mortality. A malnutrition inflammation score (MIS) has been proposed as ...

non disponibile

Background: Metformin-associated lactic acidosis (MALA) is a severe complication of drug administration with significant morbidity and mortality. So far no study in large population areas have examined the incidence, clinical profile and outcome of acute kidney injury (AKI)-MALA patients admitted in intensive care units (ICUs) and treated by renal replacement therapy (MALA-RRT). Methods: Retrospective analysis over a 6-year period (2010-2015) in Piedmont and Aosta Valley regions (5,305,940 inhabitants, 141,174 diabetics treated with metformin) of all MALA-RRT cases. Results: One hundred and seventeen cases of AKI-MALA-RRT were observed (12.04/100,000 metformin treated diabetics, 1.45% of all RRT-ICU patients). Survival rate was 78.3%. The average duration of RRT was 4.0 days at mean dialysis effluent of 977 mL/kg/day. At admission most patients were dehydrated, and experienced shock and oliguria. Conclusion: Our data showed that MALA-RRT is a common complication, needing more prevention. Adopted policy of early, extended, continuous and high efficiency dialysis could contribute to an observed high survival rate. Video Journal Club “Cappuccino with Claudio Ronco” at http://www.karger.com/?doi=471917.

We describe factors associated to renal infarction, clinical, instrumental and laboratoristic features, and therapeutic strategies too. This is an observational, review and polycentric study of cases in Nephrologic Units in Piedmont during 2013-2015, with diagnosis of renal infarction by Computed Tomography Angiography (CTA). We collected 48 cases (25 M, age 57±16i; 23 F age 70±18, p = 0.007), subdivided in 3 groups based on etiology: group 1: cardio-embolic (n=19) ; group 2: coagulation abnormalities (n= 9); group 3: other causes or idiopathic (n=20). Median time from symptoms to diagnosis, known only in 38 cases, was 2 days (range 2 hours- 8 days). Symptoms of clinical presentation were: fever (67%), arterial hypertension (58%), abdominal o lumbar pain (54%), nausea/vomiting (58%), neurological symptoms (12%), gross hematuria (10%). LDH were increased (530 UI/ml) in 96% of cases (45 cases out of 47), PCR (0.5 mg/dl) in 94% of cases (45 out of 48), and eGFR60 ml/min in 56% of cases (27 out of 48). Comparison of the various characteristics of the three groups shows: significantly older age (p=0.0001) in group 1 (76±12 years) vs group 2 (54±17 years) and group 3 (56±17 years); significantly more frequent cigarette smoking (p = 0.01) in group 2 (67%; 5 cases out of 9) and group 3 (60%; 12 cases out of 20) than group 1 (17%). No case has been subjected to endovascular thrombolysis. In 40 out of 48 cases, anticoagulant therapy was performed after diagnosis: in 12 (32%) cases no treatment, in 12 cases (30%) heparin, in 8 cases (20%) low molecular weight heparin, in 4 cases (10%) oral anticoagulants, in 3 cases fondaparinux (7%), in 1 case (2%) dermatan sulfate.Although some characteristics may guide the diagnosis, latency between onset and diagnosis is still moderately high and is likely to affect timely therapy.

We analyzed the clinical features and the factors associated with the presence of hyperkalemia (serum potassium5.3 mmol/L) in a cohort of patients presenting to an Emergency Department. A total of 168 cases were observed (89 males and 79 females), mean age 77.512 years. Fifty-six patients were diabetics (33.3%), 51 patients had chronic kidney disease (30%) and 36 patients with cardiac failure (21.4%). Sixty-nine patients (41%) were treated with RAS-blockers (ACE-I n = 50; ARBs, n = 19). 65 subjects were taking loop diuretics (39%), 17 (10%) thiazides. Thirty-one (18%) were assuming antialdosterone drugs; 16 (52%) out of these had a positive history of heart failure and 14 (41%) had a positive history of chronic kidney disease. In 85 cases (51%) patients were receiving an ACE/ARB or an antialdosterone drug. In 125 patients (74%) eGFR at presentation was60 ml/min/1.73 m2. Serum potassium values were significantly higher in patients treated with both ACE/ARB and antialdosterone drugs. In 20 cases (12%) serum potassium was 6.5 mmol/L; these patients assumed antialdosterone drugs more frequently, alone and mostly in association with ACE-I/ARBs (65% vs 7%; p0.0001). The simultaneous assumption of ACE-I/ARBs and antialdosterone drugs emerges as the major cause of severe hyperkalemia in our cases, thus confirming the warnings about this association in the presence of advanced age and reduced glomerular filtration rate.

The kidneys are a major target of PAPS. The histologic lesions of PAPS nephropathy are vascular; among them thrombotic microangiopathy (TMA) is the most characteristic. It is still not clear in the literature whether the nephropathy can be the unique manifestation of PAPS in the absence of other thrombotic processes; that is: do the renal microthrombotic lesions allow to make the diagnosis of PAPS in presence of anti-phospholipid antibodies (APA)? With this purpose we present three clinical cases. The first patient had severe hypertension C4 hypocomplementemia, thrombocytopenia, and mitralic valve insufficiency. LAC and anti-cardiolipin antibodies at high titre were positive. The histologic picture was characterized by basement membrane reduplication and arteriolar mucoid degeneration, which are features of early phase of TMA. The second patient had severe hypertension. The detection of anti-cardiolipin antibodies was performed several times and resulted positive three times, four months after the diagnosis as well. The renal histologic features were consistent with late lesions of TMA. The third patient had severe hypertension, rapidly progressive renal failure, tricuspidal valve insufficiency and two positive anti-phospholipid antibodies determinations three weeks apart (in two occasions anti-cardiolipin and in one occasion LAC as well were found). The renal lesions were characteristic for TMA. In conclusion we think that patients with TMA and antiphospholipid antibodies can be considered affected by PAPS, as the thrombotic process is represented by thrombosis in preglomerular arterioles, which leads to TMA.

The Piedmont Group of Clinical Nephrology compared the activity of 18 nephrology centers in Piedmont and Aosta Valley as regards acute pielonephritis (APN). Data from more than 500 cases per year of APN were examined. The microbial spectrum of APN consists mainly of Escherichia coli and Klebsiella pneumoniae. Diagnosis was based on both clinical and radiological criteria in most of the centers (computed tomography-CT o Magnetic Resonance Imaging-MRI). In four centers diagnosis was made with the radiological criteria and in one center only with the clinical features. CT and MRI were performed in about 47% and 44% of cases respectively. Urine culture was positive in 22 up to 100% of cases. The most commonly used antibiotics were fluoroquinolones (ciprofloxacin or levofloxacin) and ceftriaxone (50% of centers) or amoxicillin/clavulanic acid (25% of centers). In 75% of the centers, patients received a combination of two antibiotics (aminoglycoside in 22% of them ). In 72% of the centers, almost 50% of the patients were re-examined, while 38.8% of centers re-examined all the patients. Renal ultrasound was inappropriate to identify abscesses. The mean of patients in whom renal abscesses were detected by CT or MRI was 18.2%. The analysis shows a high variability in the way of diagnosing and treating APN in Piedmont and Aosta Valley regions. This suggests that even if APN is a frequent pathological condition, practical recommendations are required.

A case of splenic large B-cell lymphoma with hemophagocytic syndrome is reported. The difficulties of diagnosis are emphasized especially when peripheral lymph nodes or bone marrow lymphomatous infiltration are not present. Diagnostic criteria for hemophagocytic syndrome and their relationship with the pathogenesis of the disease are also stressed.

The aim of this study was the detection of HCV viremia in both anti-HCV antibody positive and negative hemodialysis patients. Sera from 75 patients on extracorporeal blood purification in the same dialysis unit were analyzed. Anti-HCV antibodies were detected using a 2nd-generation ELISA assay and in all positive cases a RIBA 3rd-generation test was performed. HCV-RNA was tested by a reverse transcription-nested polymerase chain reaction (RT-PCR) assay with primers located in the 5' region. PCR products were analyzed by a nonradioactive hybridation assay. The presence of anti-HCV antibodies was detected in 30 (40%) patients by means of ELISA II test; 28 of them were RIBA III positive and two indeterminate. Twenty-four of the 30 HCV Ab ELISA II positive patients (80%) were HCV-RNA positive (23 RIBA III positive and 1 indeterminate). Six anti-HCV Ab ELISA II positive patients tested negative for HCV-RNA (20%); 5 of these patients were also positive for anti-HCV antibodies with a RIBA III test and 1 was indeterminate. None of the anti-HCV negative patients was HCR-RNA positive. In two cases we documented the disappearance of viremia after an acute HCV infection, with the persistence of antibody reactivity. In conclusion, anti-HCV antibody positive hemodialysis patients should be considered as potentially infectious.

A 59-year-old man with diabetes mellitus Type II, arterial hypertension and depressive disorder was hospitalized due to unexplained severe inebriation followed by sedation. Regular medications consisted of metformin 1500 mg, enalapril 20 mg and paroxetine 20 mg. Blood tests showed a creatinine of 0.9 mg/dL (79 μmol/L), glucose 110 mg/dL (6.1 mmol/L) and potassium 6.4 mmol/L. Blood gas test showed a pronounced metabolic acidosis, with pH 7.04, bicarbonate 3 mmol/L, PCO2 10 mmHg, lactic acid 4.8 mmol/L, Na 145 mmol/L, chloride 105.4 mmol/L and anion gap 43 mmol/L. Cerebrospinal fluid analysis and cerebral computerized tomography scan were normal. The patient’s condition, including cognitive status, was rapidly deteriorating, requiring orotracheal intubation. Anuria developed in the following few hours, requiring the referral to our hospital. Laboratory data confirmed the high anion gap metabolic acidosis and showed a serum creatinine of 3.8 mg/dL (336 μmol/L). Renal replacement therapy was soon initiated with continuous venovenous haemodiafiltration; after 21 h acid–base status was normalized, but anuria persisted requiring intermittent haemodialysis. Examination of urine sediment (Figure 1) showed both needle-shaped and dumbbell-shaped calcium oxalate monohydrate crystals; these crystals are considered a clue to ethylene glycol poisoning since oxalate derives from the metabolism of ethylene glycol [1, 2]. Furthermore, renal damage most likely results from a crystal-induced injury to proximal tubule cells [3]. Fig. 1. Urine sediment showing both needle-shaped and dumbbell-shaped (upper right side) calcium oxalate dihydrate crystals. The coma lasted 2 weeks; upon regaining consciousness the patient admitted to having ingested automobile anti-freeze (containing ethylene glycol) in a suicide attempt. Progressive recovery of renal function occurred 4 weeks after admission; renal replacement therapy was interrupted 2 weeks later. A prompt examination of urine sediment, often forgotten in the current ‘high-tech’ medicine, would have suggested the correct diagnosis and allowed administration of fomepizole or ethanol to prevent brain and renal damage.

The number of immigrants has been rapidly increasing in Italy in the last decade, with potentially profound effects on the national health care system. Yet, few data are available on the clinical and demographic features of these subjects, or on their need for nephrological care and dialysis treatment. A survey was conducted in 19 dialysis facilities of Piedmont (a northwestern Italian region) about immigrants on chronic dialysis treatment. Data on native country, administrative position, clinical and dialysis aspects were anonymously collected. Overall, 93 immigrant dialysis patients coming from 24 foreign countries were registered. Most of them were young (mean age 46∓14 years) and on extracorporeal treatment (87%); late referral (38%) or starting dialysis in emergency (17%) were common modalities of presentation. Glomerular (33%) or unknown (31%) nephropathies were the most representative causes of end stage renal disease. No difference in incidence of HCV, HBV and HIV compared with native Italian patients was observed. Notably, more than 50% of the immigrant patients had low-level knowledge of Italian. As regards administrative position, 69% were regular foreign citizens, 19% were temporary foreign workers, and 9% had a residence permit. Our survey confirms the existence of a young immigrant population on dialysis in Piedmont, whose social and relational problems are more challenging than clinical aspects and call for new organizational models to manage this growing population on dialysis.

1. We evaluated the inheritance of erythrocyte Na+/Li+ countertransport activity in IgA nephropathy by assessing this parameter in 19 patients with biopsy-proven IgA nephropathy and in their 53 relatives (32 parents and 21 siblings). The possible use of erythrocyte Na+/Li+ countertransport activity as a marker of poor prognosis was also evaluated. 2. A significant correlation was found between ‘familial’ and proband Na+/Li+ countertransport activity, but not between that of spouses. 3. Mean blood pressure, although within the normal range, and Na+/Li+ countertransport activity were significantly higher in patients with proteinuria than in those without proteinuria. 4. Parents of proteinuric patients had a higher Na+/Li+ countertransport activity than parents of non-proteinuric patients. 5. In IgA nephropathy the inheritance of erythrocyte Na+/Li+ countertransport activity was preserved. Therefore genetic factors could play a role in the non-immunological progression of IgA nephropathy.

Background: We tested whether the combination of verapamil (V) or amlodipine (A) with trandolapril (T) affected proteinuria differently from T alone in patients with nondiabetic nephropathies. Methods: After T, 2 mg, in open conditions for 1 month, 69 patients were randomly assigned to be administered T, 2 mg, combined with V, 180 mg, plus a placebo or T, 2 mg, plus A, 5 mg, once a day in a double-blind fashion. Patients were followed up for 8 months. Results: Proteinuria diminished significantly after T treatment from mean protein excretion of 3,078 ± 244 (SEM) to 2,537 ± 204 mg/24 h ( P = 0.018). In the randomized phase, there was a slight reduction in proteinuria in both groups without significant differences within and between treatments (T + V, protein from 2,335 ± 233 to 2,124 ± 247 mg/24 h; T + A, protein from 2,715 ± 325 to 2,671 ± 469 mg/24 h). The selectivity index (SI; calculated as the ratio of immunoglobulin G to albumin clearance) was slightly and not significantly reduced in patients treated with T plus V from a median of 0.20 (interquartile range, 0.13) to 0.16 (interquartile range, 0.15; P = not significant), whereas it significantly increased from 0.20 (interquartile range, 0.14) to 0.30 (interquartile range, 0.14; P = 0.0001) in patients treated with T plus A. Modifications in SI and serum creatinine levels at the end of the study from randomization were significantly directly correlated ( r = 0.45; P = 0.001). The number of patients reporting adverse effects was significantly higher in the T plus A than T plus V group (63.8% versus 33.3%; P = 0.016). Conclusion: In patients with nondiabetic proteinuric nephropathies treated with T, the combination of V or A does not significantly increase its antiproteinuric effect.

The effectiveness of percutaneous revascularisation (PTRA) in the treatment of atherosclerothic renovascular nephropathy (ARN), a leading cause of progressive renal failure, is still a matter of debate.we reviewed 52 patients submitted to selective stenting from 1991 to 2000 because of ARN, followed for a mean of 22.3 months before and 24.6 after the procedure, looking for complications, re-stenosis rates, blood pressure, renal function and survival.Arterial patency was achieved in 97.1% of procedures (71.6% by stent deployment); complications occurred in 42% of patients, and re-stenoses in 17.3% of vessels, most often in those without a stent (31.6% vs 8.3%). No effect was detectable on hypertension and renal failure in the whole group, but in the subgroup without technical failure or early dialysis start PTRA reduced the creatinine clearance (BCRC) decline from 0.9 to 0.19 mL/min/month. At univariate analysis, BCRC outcome was better in bilateral or single kidney stenoses, proteinuria1 g/day, serum creatinine4 mg/dL and resistance index0.8. Survival was 68.9% at five years, with a mortality rate of 4.5/100 person-years.Renal outcome of successful PTRA differs from case to case, but efficacy is substantial. Primary stenting in ostial stenosis and selection of patients based on prognostic factors seem likely to improve the effectiveness.

Cardiovascular disease accounts for almost half of the total mortality in patients with end stage renal disease (ESRD). It has recently been debated whether coronary revascularization has the same rate of risks and successes in this cohort of patients compared to patients without renal disease. Since 1991, 17 dialysis patients were submitted to coronary revascularization in our center. Seven patients were following peritoneal, 10 hemodialytic treatment. Four patients were submitted to percutaneous transluminal coronary angioplasty (PTCA) and 13 to surgical revascularization (CABG). In 2 patients the coronary lesion was unique, in the others stenosis of multiple vessels were found. Six patients were diabetic. The mean age at the onset of the coronary artery disease (CAD) was 57.17 +/- 11.6 years. The mean time elapsed from the onset of the CAD and the performance of the PTCA or CABG was 30.1 +/- 35.4 months. The mean time from beginning of dialysis treatment to revascularization was 48.2 +/- 39.6 months. Mean hemoglobin values were 9.7 +/- 1 g/dL, mean phosphorus values were 5.2 +/- 8.7 mg/dL, mean cholesterol values were 211 +/- 49.5 mg/dL. The procedure was technically successful in all patients. Mean survival was 25.09 +/- 28.12 months. Twelve patients died, 5 of whom within one month. Survival at one month was 70.5%, at 6 months 58.8%, at one year 52.9%, at 2 years 47%. There was neither significant difference patients submitted to PTCA and those submitted to CABG, nor between diabetic and non-diabetic patients. In conclusion, coronary revascularization in our experience is a high risk procedure in dialysis patients. The reasons for this could be the severe general conditions of these patients affected with diffuse vasculopathy and the long time elapsed since the onset of the ischemic cardiopathy. Thus, our results could suggest the opportunity of performing earlier screening of coronary situation and revascularization treatment in CAD dialysis patients.

dialysis strategies and pharmacological management of hypertension. Background. The tenet that peritoneal dialysis is capable of either normalizing or improving blood pressure Key words: ambulatory blood pressure monitoring; control in uraemic patients is based on outdated or antihypertensive therapy; prevalence of hypertension; monocentric experiences. Therefore, we assessed the peritoneal dialysis; white-coat hypertension prevalence of hypertension and the eYcacy of antihypertensive therapy in a large, multicentric cohort of patients on peritoneal dialysis. Methods. Twenty seven out of the 50 centres belonging Introduction to the Italian Co-operative Peritoneal Dialysis Study Group took part in the study. The main patient Cardio- and cerebrovascular events are the main causes selection criteria were: peritoneal dialysis therapy for of morbidity and mortality of patients on peritoneal at least 3 months and no peritonitis or changes in dialysis [1]. Although high blood pressure (BP) is the dialysis technique for at least 1 month. Clinical blood leading factor causing cardiovascular mortality in the pressure was measured according to WHO/ISH general population, scant attention is paid to arterial guidelines. Ambulatory blood pressure monitoring hypertension in recent peritoneal dialysis studies. This was carried out using a SpaceLabs 90207 recorder. might be due to the general belief that end-stage renal Hypertension was defined according to WHO/ISH disease (ESRD)-related hypertension is easily concriteria and staged according to the criteria of the Joint trolled by peritoneal dialysis. Unfortunately, this asserNational Committee on Detection, Evaluation and tion is at least in part based on outdated reports [2]. Treatment of High Blood Pressure (JNC ), 5th Report. In recent years, ambulatory blood pressure monitoring Ambulatory blood pressure monitoring recordings has been applied in peritoneal dialysis patients. This were used to evaluate white-coat hypertension, blood evaluation technique oVers some advantages over trapressure load and the dipping phenomenon. ditional oYce measurement as it avoids ‘observer bias’, Results. Five hundred and four subjects were evalu- ‘digit preference’ of the operator and the stress reaction ated. Hypertension was prevalent in 88.1% of the of the patient, and provides mean BP levels represpopulation, and 362 out of 444 hypertensive patients enting the average of >90 measurements per day. were on antihypertensive therapy. JNC staging Nonetheless, only a few small studies have been carried revealed that 188 patients had moderate to severe out using ambulatory blood pressure monitoring in hypertension. Blood pressure load was pathological in peritoneal dialysis patients [3]. 77.3% of the patients receiving antihypertensive treat- We were thus prompted to conduct a large multicenment. White-coat hypertension was identified in 9.1% tre study to evaluate the prevalence of hypertension of the hypertensive patients not on antihypertensive and the eYcacy of antihypertensive therapy in peritontherapy, and 53.1% of the patients were non-dippers. eal dialysis patients using traditional clinical sphygmoConclusions. The study demonstrates that hyper- manometric measurements and 24 h ambulatory blood tension is a dramatic, unsolved problem in uraemic pressure monitoring recordings. patients treated with peritoneal dialysis, and casts doubts on the eVectiveness of our current peritoneal Subjects and methods

In this paper we report some results of our studies on patients with immunoglobulin (Ig)A nephropathy regarding (1) the familiar aggregation of erythrocyte sodium-lithium (Na,Li) countertransport; (2) the association of Na,Li countertransport with the presence of arterial hypertension and lipid abnormalities; (3) the correlation between Na,Li countertransport activity and renal functional reserve; and (4) the preliminary results of a longitudinal study. In 13 families of patients with IgA nephropathy, selected because both parents were available, we found a significant correlation between midparent and offspring Na,Li countertransport activity (Spearman's rank correlation = 0.65; P = 0.023), but no husband-wife relationship. In 49 patients, the activity of Na,Li countertransport was significantly higher in erythrocytes from 20 hypertensive patients than from either 29 normotensive patients or from 36 healthy age- and sex-matched normal subjects. Hyperlipidemic patients had an erythrocyte Na,Li countertransport activity significantly higher than normolipidemic patients and controls. In 17 patients a significant inverse correlation was found between the peak variation of creatinine clearance over baseline value after an oral protein load and the erythrocyte Na,Li countertransport activity (Spearman r = 0.54; P = 0.03). In a longitudinal study of 36 patients followed from 12 to 36 months, those showing a progression toward renal failure had an erythrocyte Na,Li countertransport activity higher than median value. The results of our studies show that in patients with IgA nephropathy a high erythrocyte Na,Li countertransport rate, genetically determined, is associated with the presence of arterial hypertension and lipid abnormalities, and perhaps with a less favorable disease outcome.

Increased sodium-lithium countertransport activity in red cells of IgA nephropathy patients. The aim of this work was to analyze Na,Li countertransport activity in the erythrocytes from patients with IgA nephropathy, in relationship with their blood pressure status and lipid profile Forty-nine patients (32 males, 17 females) with biopsy-proven IgA nephropathy and without significant impairment of renal function (serum creatinine ≤ 1.4 mg/dl) and 36 normal subjects (21 males, 15 females) were evaluated Twenty-nine patients with IgA nephropathy were normotensive and 20 hypertensive (diastolic pressure ≥ 95 mm Hg or treated by antihypertensive drugs). Na,Li countertransport was significantly higher in red cells from hypertensive than from normotensive patients (P = 0.002) and normal subjects (P = 0.0001), (values respectively 309 ± 17; 241 ± 12 and 211 ± 11 µmol/liter RBC/hr); normotensive patients with IgA nephropathy did not differ from controls regarding the Na,Li countertransport rate. A multiple stepwise logistic regression analysis with blood pressure status as the dependent variable and Na,Li countertransport activity, age, serum creatinine, proteinuria, cholesterol, triglycerides, plasma potassium and time from onset as independent variables, indicated an independent significant association for Na,Li countertransport (P = 0.002) proteinuria (P = 0.006), plasma potassium (P = 0.006) and age (P = 0.029). Other tested variables were not independently related to blood pressure status. Hyperlipidemic patients (plasma total cholesterol concentration >200 mg/dl and/or plasma triglycerides >172 mg/dl) had an erythrocyte Na,Li countertransport activity significantly higher than normolipidemic (P = 0.005) and controls (P = 0.001) (values respectively 295 ± 14; 226 ± 12 and 211 ± 11 µmol/liter RBC/hr). A high erythrocyte Na,Li counter-transport rate may be a marker of an increased risk of developing arterial hypertension, lipid abnormalities, and perhaps a more severe renal disease in IgA nephropathy.

The aim of this study was to analyze Na,Li countertransport in erythrocytes from adolescents with insulin dependent diabetes mellitus (IDDM) and to see if those with elevated values present distinct clinical features, in particular as regards arterial pressure and urinary albumin excretion (UAE). Twenty-nine adolescents with IDDM (17 males, 12 females, mean age 15 +/- 0.6 years, mean diabetes duration 11.4 +/- 0.7 years) and fifteen healthy age-matched control subjects (8 males, 7 females, age 14.5 +/- 1 years) were investigated. Diabetic adolescents had a RBC Na,Li countertransport activity higher than age matched normal controls; geometric mean 283 (95% limits 259-340) vs. 193 (169-252) mumol/l RBC/h; p less than 0.01. Seven out of 29 subjects had values higher than the 95th percentile of normal subjects (Counter +). Both systolic and diastolic arterial pressures were significantly higher in Counter + than in Counter - patients. No significant differences were found as regards age, body mass index, diabetes duration, HbA1c, fructosamine, serum potassium, triglycerides, creatinine clearance and UAE. The logarithm of systolic pressure was independently positively correlated with ln Na,Li countertransport (r = 0.38; p less than 0.05), ln [Nai] (r = 0.38; p less than 0.05), and ln body mass index (r = 0.5; p less than 0.01) in diabetic patients. The main finding of this study is that diabetic adolescents with a high erythrocyte Na,Li countertransport rate have an arterial pressure significantly higher than patients with normal Na,Li countertransport fluxes.

The intracellular concentration of Na+ ([Na+i]) and the Na+ efflux mediated by the Na+, K+ pump were evaluated in red blood cells from 9 patients on hemofiltration, 8 on hemodialysis, 9 on continuous ambulatory peritoneal dialysis (CAPD) and 12 normal subjects. [Na+i] was elevated in CAPD patients only. The rate constant for pump-mediated sodium efflux was close to normal in hemofiltration patients, and significantly reduced in hemodialysis (p +, K+ pump activity of normal red blood cells. Among our uremic patients those on hemofiltration showed a red blood cell Na+, K+ pump activity close to that of normal subjects, possibly related to the absence in their plasma of a circulating pump inhibitor, that seems invariably present in plasma from hemodialysis and CAPD patients.

The acute effects of both acetate and bicarbonate hemodialysis on erythrocyte transmembrane sodium fluxes were investigated in 15 patients with chronic uremia. We observed a significance (p less than 0.01) stimulation of the Na+,K+ pump in both procedures, with a significant correlation to the amount of fluid removed during hemodialysis (r = 0.56, p less than 0.03). Outward Na+ cotransport fluxes significantly rose (p less than 0.05) after acetate hemodialysis and decreased (p less than 0.05) after bicarbonate hemodialysis. Minor and not significant pre- and posthemodialysis bidirectional changes were observed as regards the intraerythrocyte Na+ and K+ concentration, passive Na+ and K+ permeability, and Na+,Li+ countertransport. Hemodialysis may acutely affect the erythrocyte sodium pump and cotransport fluxes, possibly through the modulation of hormonal factors triggered by the extracellular volume changes.

Erythrocyte Na,K pump activity and arterial hypertension in uremic dialyzed patients. We have evaluated in 26 uremic patients [21 on hemodialysis, 5 on continuous ambulatory peritoneal dialysis (CAPD)], 11 normotensive, and 15 hypertensive (MAP > 110mm Hg) patients the following properties: a) erythrocyte (RBC) Na concentration [Nai] and ouabain-sensitive and -resistant Na effluxes; b) the effect of uremic sera on ouabain-sensitive Na efflux in normal RBC; c) serum digoxin-like immunoreactivity; d) cardiac index and total peripheral resistance. In 19 healthy subjects a) and c) were also evaluated. RBC Na,K pump activity was lower in uremic patients than in normal subjects (P < 0.0005), and lower in hypertensive (P < 0.02) than in normotensive patients. Serum from uremic patients inhibited ouabain-sensitive Na efflux in normal RBC, the inhibition being correlated with both the rate constant for ouabain-sensitive Na efflux (r = -0.67; P < 0.005) and [Nai] (r = 0.43; P < 0.05) of RBC of patients from whom the serum was obtained. Inhibition of ouabain-sensitive Na efflux was significantly higher with serum from hypertensive than from normotensive patients (P < 0.05). Serum digoxin-like immunoreactivity was present in all uremic patients (0.402 ± 0.054 ng/ml in normotensive and 0.428 ± 0.040 ng/ml in hypertensive, P = ns), while it was not detectable in normal subjects. Hypertensive patients had peripheral resistance significantly higher than normotensive (P < 0.05), while cardiac index was similar in both groups. A strong inverse correlation was found between the rate constant for ouabain-sensitive Na efflux in RBC and total peripheral resistance (r = -0.76; P < 0.0001). In conclusion: 1) Hypertensive uremic dialyzed patients have lower erythrocyte Na,K pump activity as compared with normotensive, and higher levels of a specific circulating Na,K pump inhibitor; 2) reduced sodium transport by Na,K pump is strongly correlated with increased total peripheral resistance, thus suggesting a role in the pathogenesis of arterial hypertension in patients with chronic uremia undergoing hemodialysis or CAPD; 3) a digoxin-like immunoreactive material is detectable in uremic sera, but it does not have a close relationship to Na,K pump inhibitor.

1. Intracellular Na+ concentration [Na+]i and Na+ extrusion catalysed by sodium, potassium-activated adenosine triphosphatase (Na+, K+-pump) were evaluated in erythrocytes from 21 obese children and 20 normal weight- and age-matched controls. 2. Obese children showed a significantly decreased Vmax for Na+, K+-pump-mediated Na+ efflux (5638 ± 338 vs 7597 ±335 μmol h−1 litre−1 of cells mean±SEM, P = 0.01), while [Na+]i (9.3±0.3 vs 9.1 ± 0.5 mmol/litre of cells, mean±SEM, NS) and Na+ efflux in fresh cells (2380± 153 vs 2533 ± 180 μmol h−1 litre−1 of cells, mean ±sem, NS) were similar in both groups. 3. Mean diastolic blood pressure was significantly higher in obese children than in controls, although both groups were normotensive (73.8 ± 1.3 vs 66.2 ±1.9 mmHg, mean ± sem, P = 0.009). 4. Abnormal Na+, K+-pump activity is present in individuals with idiopathic obesity. 5. The possible link between obesity and blood pressure regulation may be mediated through modifications in Na+, K+-pump activity.

Canrenone is the main active metabolite1 of the diuretic and antihypertensive drugs spironolactone and canrenoate-K, and competes with aldosterone for a common cytosolic receptor in distal and collecting tubules of the nephron.2 In addition it has recently been demonstrated that canrenone in vitro may directly interfere with ouabain-sensitive Na+,K+ pump (Na+,K+ adenosine triphosphatase), acting as a partial agonist at the digitalis receptor site. 3,4 Moreover Garay et al.4 showed that canrenone is able to restimulate in vitro the Na+,K+ pump of human red blood cells (RBC) blocked by high concentrations of ouabain.

1. The effects of a 2 litre intravenous infusion of saline (0.9% NaCl solution) over 3 h on erythrocyte transmembrane sodium transport were studied in 12 normal human subjects. 2. After saline infusion a significant (P < 0.01) reduction of both outward Na+, K+ pump- and Na+, K+ cotransport-mediated Na+ effluxes was observed. The Na+, Li+ countertransport rate and the passive Na+ permeability did not change. 3. The incubation of the subjects' erythrocytes, obtained on a separate occasion, with their own plasma taken after the saline infusion, induced an inhibition of both Na+, K+ pump and Na+, K+ cotransport outward sodium fluxes. The percentage decrease after incubation was closely correlated with the percentage reduction induced by the saline infusion in vivo (r = 0.93 for the pump and r = 0.96 for cotransport; P < 0.01). 4. These data suggest that extracellular fluid volume expansion affects the release of circulating factors modulating sodium transport by the Na+, K+ pump and by Na+, K+ cotransport.

In 38 uraemic dialysed patients (17 normotensive, 21 hypertensive) we measured (1) erythrocyte sodium concentration [Nai] and ouabain-sensitive sodium efflux, and (2) arterial pressure, cardiac index and total peripheral resistance. Erythrocyte Na-K pump activity was lower in hypertensive than in normotensive patients (P less than 0.02). Hypertensive patients had significantly higher peripheral resistance than normotensive patients (P less than 0.05), while the cardiac index was similar in both groups. Inverse correlations were found between the rate constant for ouabain-sensitive sodium efflux in erythrocytes and both systolic and diastolic pressure (r = -0.43 and r = -0.45, respectively; P less than 0.01) and total peripheral resistance (r = -0.76; P less than 0.0001). Our data suggest that reduced sodium transport by the Na-K pump plays a role in the pathogenesis of arterial hypertension in patients with chronic uraemia.